Our long-term objective in this investigation is to delineate the critical three-dimensional structural features which are required for the control of specificity and the generation of reactivity in both co- and post-translational modification reaction. We plan to initiate our investigations with the in-depth examination of the following enzyme catalyzed derivatization reactions; the N- asparagine-linked glycosylation, mediated by glycosyl transferases, and the cAMP-dependent phosphorylation mediated by a protein kinase. The first process is co-translational and the second post- translational. Since enzyme-cataly derivatization of proteins is central to innumerable biological control processes, an understanding of the manner in which specificity is achieved in these reactions is of clear importance both to fundamental biochemistry and in a practical consideration of the mechanisms of homeostatic control. The experimental approach in the investigation is a multidisciplinary one and incorporates both the design and synthesis of substrate analogues of well-defined three-dimensional structure, as well as the investigation of these analogues using biochemical techniques. The substrate analogues would, in the initial phase be based on peptidyl structures, which incorporate features such as conformational restrictions, reporter groups or affinity labels. From the information obtained from this phase of the work we could then design and synthesize non-peptidyl mimics of the modified sequences. In these compounds we could truly identify the precise features controlling recognition independent of the supporting peptide framework.